Malignant Epithelial Mesothelioma

The characteristics of your cancer, even at the cellular level, can have a huge impact on your prognosis. Learn about epithelial mesothelioma, a common cell type that responds especially well to treatment.

Epithelial mesothelioma accounts for 50 to 70 percent of all diagnosed cases.

The cellular makeup of a mesothelioma tumor can vary substantially from patient to patient. Malignant epithelial mesothelioma, a specific cellular type of the disease, accounts for 50 to 70 percent of all diagnosed cases. If your tumor is mainly composed of epithelial cells, you may respond better to treatment and receive a more favorable outcome than patients with other cell types. Knowing its characteristics, how it is diagnosed and its most effective treatment options will help you understand how cell type can affect your prognosis.

Because it represents the majority of cases, doctors have performed more research on epithelial mesothelioma than any other cell type. During cancer research, doctors study cell types to better understand how well patients will respond to specific treatments. Although treatment does not typically differ from one cell type to the next, your type may dictate which clinical trials are available to you.

Characteristics

Tumors can be classified by the type and appearance of the cancerous cells involved. Epithelial cells form the epithelium, which is the most common of the four major tissue types in humans. With functions including protection, sensory perception and fluid secretion, epithelial tissue lines several major body cavities and most of our organs. Epithelial cells are also present in our skin, eyes, taste buds and ears.

The structure of epithelial tissue will vary depending on its location and function. The epithelial cells may appear thin and flat, cube- or hexagon-shaped or tall and column-like. When the epithelial cells turn cancerous, they can take on several visual patterns. Usually they lose uniformity or otherwise become atypical in appearance, but they can also form small tubes or clusters that resemble a raspberry. Once epithelial cells become cancerous they are called epithelioid cells. Epithelioid cells occur more commonly in cases of malignant pleural mesothelioma rather than peritoneal mesothelioma.

Because epithelial cells lack mobility and adhere closely together, they are less likely to spread to distant locations like sarcomatoid cells. Cancerous epithelial cells primarily spread to nearby lymph nodes and from there migrate locally via the lymphatic system. Conversely, sarcomatoid cells are loosely organized, and they can migrate easily, leading to quicker metastasis.

How It Is Diagnosed

Epithelial cancer cells cannot be identified with diagnostic imaging scans. To determine which cell type is present, a thoracoscopy or similar form of surgical biopsy needs to be performed. Biopsies offer doctors a way to examine the potentially cancerous cells under a high-powered microscope. During a biopsy, a tissue sample of the tumor is extracted for further evaluation of the cells it contains.

One of the primary challenges of diagnosing epithelioid mesothelioma is distinguishing it from other types of cancer. Epithelial tumors are often confused with adenocarcinoma, a common type of cancer that develops in the lungs, breasts and colon. Glandular mesothelioma, an epithelial cell subtype, may resemble adenocarcinoma of the lungs. It may be difficult to differentiate these two conditions.

Immunohistochemistry

Immunohistochemistry is a process that detects proteins called antibodies on the surface of cells. These proteins help classify a cancer’s cell type. Pathologists use immunohistochemistry to identify epithelial mesothelioma and differentiate it from adenocarcinoma. Immunohistochemistry is used less often to differentiate sarcomatoid mesothelioma from other sarcomatoid tumors.

Some of the antibodies that help diagnose epithelial mesothelioma include calretinin, CK5/6, WT-1, D2-40, TTF-1 and BerEP4. Calretinin is considered the most sensitive and specific antibody for mesothelioma. It is present in the majority of epithelial mesothelioma cases.

The specific cell type will be revealed in your doctor's pathology report. If you haven't been told your cell type yet, just ask your doctor and request a copy of the pathology report for your records.

Defining Characteristics

Epithelial mesothelioma has many subtypes, each with its own unique characteristics. Some subtypes are more likely to develop in specific parts of the body, while others are extremely rare. While the subtype you have won’t affect your treatment, it does help doctors tell mesothelioma apart from similar looking cancers.

The following are technical descriptions of some cell patterns doctors have observed in cases of epithelial mesothelioma.

Tubulopapillary

The tubulopapillary cell pattern is one of the most common subtypes of epithelial mesothelioma. These tumors contain a mixture of small tubules and papillary structures with fibrovascular cores. Lining the papillary structures are small to medium-sized cuboidal cells with mostly uniform and round nuclei. Small to medium-sized nucleoli appear within the nuclei.

Most tubulopapillary mesotheliomas contain well-differentiated cells, but may be formed by anaplastic cells in some cases. Psammoma bodies may be present, but they appear less frequently than in other papillary carcinomas, such as serous papillary carcinoma of the peritoneum. Doctors may mistake this subtype for adenocarcinoma that has spread to the pleura.

Adenomatoid

Adenomatoid mesothelioma, also known as the microglandular subtype, accounts for 6 percent of all pleural mesothelioma cases. These tumors are made of bland cells that are flat to cube-like in shape and lined by small gland-like structures.

They often appear alongside other subtypes, but may also be the dominant cell pattern. It can be difficult for doctors to tell this subtype apart from other tumors, including benign adenomatoid tumors and metastatic adenocarcinoma of the pleura.

Solid

The solid subtype has two patterns: Well-differentiated and poorly differentiated.

Solid well-differentiated is one of the most common cell patterns seen in mesothelioma. Its round cells form nests, cords or sheets. Cellular features include round, vesicular nuclei, abundant cytoplasm and prominent nucleoli.

The poorly differentiated pattern has relatively unorganized cells that are polygonal to round in appearance. Nuclei are uniform and mostly arranged in monotonous sheets.

Solid well-differentiated mesothelioma may be mistaken for benign reactive mesothelial hyperplasia, while the poorly-differentiated pattern appears similar to lymphoma and large cell carcinoma.

Glandular

Tumors with the glandular pattern are mostly composed of acinar, or gland-like structures. The lumina appear extended or branching and are usually lined by relatively uniform and bland cuboidal cells. This subtype usually develops in the pleural lining. It may be confused for adenocarcinoma that has spread to the pleura.

Deciduoid

Deciduoid mesothelioma is a rare epithelial subtype that may be caused by factors other than asbestos exposure. This pattern features large, round to polygonal cells with sharp borders. The cytoplasm, abundant and glassy, absorbs eosin dye. Nuclei are round and vesicular with prominent nucleoli, much like an exuberant decidual reaction.

Because it is so uncommon, deciduoid mesothelioma can be mistaken for other conditions, including squamous cell carcinoma, anaplastic large cell lymphoma, gastrointestinal autonomic nerve tumor, pseudotumoral deciduosis, trophoblastic neoplasia and the oxyphilic variant of ovarian clear cell carcinoma.

Other Subtypes

Epithelial cells may even be further classified as one of the following subtypes:

Small Cell

It's sometimes mistaken for small cell lung cancer. Small cell mesotheliomas feature small, round cells that are uniform in appearance.

Cystic

Cystic mesotheliomas usually develop in the peritoneum and may be benign or noncancerous. Subtypes include multicystic, adenoid cystic, macrocystic and microcystic.

Clear Cell

Made of clear, polygonal cells, this rare subtype may be mistaken for renal cell carcinoma.

Glomeruloid

This uncommon subtype, characterized by round or oval-shaped cells, may not be linked to asbestos exposure.

Mesothelioma In Situ

Mucin Positive

Tissue staining reveals the presence of mucin in 2 to 5 percent of epithelial cases.

Histiocytoid

This rare subtype is made of cells resembling pulmonary macrophages.

Poorly Differentiated

Also called pleomorphic mesothelioma, this subtype features large cells that are round, polygonal or irregularly shaped.

Well-differentiated Papillary Mesothelioma

A slow-growing variant that is not prone to spread, well-differentiated papillary mesothelioma features papillae lined by a single layer of flat mesothelial cells.

Signet Ring

This rare subtype usually develops in the peritoneum and may be mistaken for signet ring carcinoma.

Single File

This subtype, named for its single file cell pattern, may be mistaken for metastatic lobular carcinomas of the breast.

How Epithelial Cells Affect Treatment

Because epithelioid cells respond best to treatment, a patient with this type may be considered for a more aggressive mesothelioma treatment plan. Epithelial mesothelioma patients diagnosed before the cancer has spread throughout the chest often qualify for multimodal therapy, which attempts to kill cancer cells with multiple therapies. Multimodal therapy combines the most effective anti-cancer treatments for mesothelioma, including surgery, chemotherapy and radiation therapy.

In 1999, Dr. David Sugarbaker published impressive survival results among a group of pleural mesothelioma patients with epithelial cell type who had multimodal therapy that included an extrapleural pneumonectomy surgery, chemotherapy and radiation therapy. About 46 percent of patients who had epithelial cell type, no lymph node involvement and no remaining cancer cells after surgery lived at least five years. The typical five-year survival rate for mesothelioma is around 10 percent.

How Epithelial Cells Effect Prognosis and Survival

The presence of purely epithelial cells usually supports a better prognosis than sarcomatoid and biphasic subtypes. The median survival time of patients with epithelial mesothelioma is about one year after diagnosis. The improved prognosis is around 200 days, but it could amount to years if the cancer is diagnosed in an early stage.

In 1996, a now well-known Swedish study examined tumor cell type as a prognostic factor in 85 cases of pleural mesothelioma. Patients with epithelial mesothelioma survived about 200 days longer than patients with sarcomatoid or biphasic cell types. Those with tubulopapillary cells, a subtype of epithelial mesothelioma, lived 275 days longer than patients with other cell types.

Overall, epithelioid mesothelioma is associated with better response to treatment and longer survival. This cell type can open a window for patients to access aggressive treatment plans and innovative clinical trials.